A longitudinal study assessing the impact of elexacaftor/tezacaftor/ivacaftor on gut transit and function in people with cystic fibrosis using magnetic resonance imaging (MRI)
Copyright policy )A longitudinal study assessing the impact of elexacaftor/tezacaftor/ivacaftor on gut transit and function in people with cystic fibrosis using magnetic resonance imaging (MRI)
Gastrointestinal (GI) symptoms in cystic fibrosis (CF) are common and disruptive. The effect of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on the GI tract is not fully understood. The aim was to use magnetic resonance imaging (MRI) to determine if elexacaftor/tezacaftor/ivacaftor (ETI) changed GI function and transit.This was an 18 month prospective, longitudinal, observational study. We enrolled 24 people with CF aged 12 years or older to undergo MRI scans before starting ETI and 3, 6, and 18 months after starting ETI. The primary outcome measure was change in oro-caecal transit time (OCTT) at 6 and 18 months. Secondary outcome measures included change in small bowel water content (SBWC), change in the reduction in small bowel water content following a meal (DeltaSBWC) and change in total colonic volume (TCV).A total of 21 participants completed MRI scans at 6 months and 11 completed at 18 months. After 18 months of ETI, median OCTT significantly reduced, from >360 min [IQR 240->360] to 240 min [IQR 180-300] (p = 0.02, Wilcoxon signed-rank). Both SBWC and DeltaSBWC increased after starting ETI. TCV reduced significantly after 18 months (p = 0.005, Friedman).Our findings suggest an improvement in small bowel transit, small bowel response to food and a reduction in colonic volume after starting ETI. These effects may relate to CFTR activation in the small bowel. To our knowledge this is the first study to show a physiological change in GI transit and function in response to CFTR modulator use through imaging studies.
- Queen's University Belfast United Kingdom
- National Institute for Health Research United Kingdom
- University Hospital of Lausanne Switzerland
- Nottingham University Hospitals NHS Trust United Kingdom
- University of Nottingham United Kingdom
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Male, Adult, Indoles, Cystic Fibrosis, Adolescent, Pyridines, 610, Humans; Cystic Fibrosis/drug therapy; Cystic Fibrosis/physiopathology; Male; Female; Magnetic Resonance Imaging/methods; Benzodioxoles/therapeutic use; Gastrointestinal Transit/drug effects; Longitudinal Studies; Prospective Studies; Aminophenols/therapeutic use; Adult; Pyrazoles/therapeutic use; Pyrazoles/pharmacology; Indoles/therapeutic use; Adolescent; Drug Combinations; Chloride Channel Agonists/therapeutic use; Quinolones/therapeutic use; Pyridines/therapeutic use; Pyridines/pharmacology; Cystic Fibrosis Transmembrane Conductance Regulator; Child; Quinolines/therapeutic use; Quinolines/pharmacology; Young Adult; Pyrrolidines/therapeutic use; CF; CFTR modulator; Cystic fibrosis; ETI; GI; MRI; elexacaftor/tezacaftor/ivacaftor; gastrointestinal; gut; magnetic resonance imaging, Cystic Fibrosis Transmembrane Conductance Regulator, name=Pediatrics, Quinolones, Aminophenols, Cystic fibrosis, /dk/atira/pure/subjectarea/asjc/2700/2740, /dk/atira/pure/subjectarea/asjc/2700/2740; name=Pulmonary and Respiratory Medicine, magnetic resonance imaging, Humans, Benzodioxoles, Longitudinal Studies, Prospective Studies, Gastrointestinal Transit, Chloride Channel Agonists, Child, name=Pulmonary and Respiratory Medicine, CFTR modulator, CF, Perinatology, gastrointestinal, Magnetic Resonance Imaging, GI, and Child Health, elexacaftor/tezacaftor/ivacaftor, Drug Combinations, /dk/atira/pure/subjectarea/asjc/2700/2735; name=Pediatrics, Perinatology, and Child Health, ETI, /dk/atira/pure/subjectarea/asjc/2700/2735, gut, Pyrazoles, Female, MRI
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